Treating pancreatic tumours may have revealed cancer's master switch
90 points by andsoitis 4 hours ago | 21 comments

gcanyon 2 hours ago
As is often the case, the title is hyperbolic. The discovery applies to 20% of tumors, and "one of cancer's significant defenses" or "a key weakness of cancer" would be more accurate.

That said, I'll happily take "we discovered a key weakness in 20% of cancers," please and thank you.

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basisword 2 hours ago
What does this mean in layman's terms? How will this potentially help me if I get cancer?
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epistasis 44 minutes ago
Cancer is not one thing, it's a huge zoo of many many many ways that cells start to break the social contract and divide in an uncontrolled manner.

One of the most commonly observed broken mechanisms is mutation in the gene KRAS that turns this on/off growth switch into the permanently on position.

This has been known for decades, of course. And there have been huge amounts of effort to try to develop drugs that target KRAS in cancer, but for decades it's always been thought of as 'undruggable' because of the difficulty of finding any molecules that would affect it.

This new drug, that finally treats KRAS mutated cancers, goes about it in a new way. Instead of trying to gum up the works of a single protein by sticking a small chemical in it, it effectively "glues" the KRAS protein to another protein, CypA, which keeps the switch away from reaching the normal areas where it's "on switch" activity works.

So this new drug means two things: 1) a lot of the most difficult to treat cancers are now far more treatable, and in the next 1-5 years clinical trials will tell us which cancers this particular drug works well for, 2) there's an entire new class of drug activity that everybody is chasing at this very moment, so in 5-25 years we'll likely have a huge number more of these sorts of treatments.

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bad_username 18 minutes ago
> Cancer is not one thing,

I know this is a popular "well actually" to do, but it is not always useful in a conversation. Yes, all cancers are different, but yes, cancer is also one thing: unchecked, harmful division of cells.

Bacteria are also all different, but still they are "one thing", and despite their diversity, antibiotics exist that can deal with many species of them at once. It is reasonable to talk about bacteria and antibacterial medications, it is also reasonable to talk about cancer and cancer treatment. I truly hope cancer will meet its "penicillin" one day (yes I know this is unlikely).

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bruce511 2 minutes ago
I understand where you are coming from here, but I think it is helpful for people to overtly grasp that there are very different cancers, very different treatments, and indeed very different outcomes.

Without this understanding it becomes a quick jump from "we're spending all this money on cancer" to "we've made no progress"

An example of the nuance plays out in the common cancers (like breast and prostrate). These have between 90 and 100% 5 year survival rates. Others (like the one in this article, pancreatic) have very poor survivability.

As you note, it's very unlikely that we'll "cure cancer". But we already "cure" (for some definition of cure) some cancers. Progress is slow, methodical, and incremental. It can feel like a lost cause when viewed from afar, but up close very real progress is being made. And that's an important message to pass along.

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dpark 6 minutes ago
It seems relevant here because the question was “How will this potentially help me if I get cancer?” and the answer is “Not at all unless you get a particular form of cancer that this applies to”.

> Bacteria are also all different, but still they are "one thing", and despite their diversity, antibiotics exist that can deal with many species of them at once.

Except people don’t ask “what if I get bacteria” the way they ask about cancer. If the story was about a new antibiotic that only affected 20% of common infectious bacteria strains and someone asked “in laypersons terms, how will this help me if I get a bacterial infection”, it would be appropriate to clarify that it only applies to some bacteria.

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LoganDark 3 minutes ago
> Except people don’t ask “what if I get bacteria” the way they ask about cancer.

Yeah, but doctors also don't tell people "you have bacteria" or claim "we found a cure for bacteria". The lack of nuance on average is largely due to a lack of nuance from experts.

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oh_my_goodness 34 minutes ago
>a lot of the most difficult to treat cancers are now far more treatable, and in the next 1-5 years clinical trials will tell us which cancers this particular drug works well for,

Can you help disambiguate this? Are there treatments now, or are there potential treatments with trials in 1-5 years?

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epistasis 7 minutes ago
The next 1-5 years will tell us which cancers this new drug will work well on, right now it's only been tried in pancreatic cancer when people have failed their first treatment. The new drug from the article, daroxonrasib, has nine trials i see currently, here:

https://clinicaltrials.gov/search?intr=daraxonrasib&viewType...

The first two are the trial that just completed and showed success: people that have pancreatic cancer that failed other treatments, then a "trial" that is meant to give quick access to more people now that it's been shown to work.

Then there's a trial for using it as the first-line treatment for pancreatic cancer, one for lung cancer (NSCLC), and also various combinations with other drugs. I expect we'll see a ton of new trials registered in the coming year. Especially something in combination with colon cancer, because a common drug resistance mechanism in colon cancer is to develop KRAS mutation.

The thing is that we don't really know which cancers it will work well in until we try. And there's limited number of people with cancer that enter clinical trials, and we want to give each person their very best chance at survival, and then there's the massive expense of running the clinical trial itself, so learning happens slowly, one month of survival at a time, or one cancer recurrence at a time, or one death at a time. Patients that take part in clinical trials really are the heroes here. (Especially with the side effects of this new drug, which are horrible. It is a revolutionary drug, but we need to learn how to manage the other things it does as well, and that's going to take time.)

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memonkey 17 minutes ago
I think the meaning is that because we can see success with KRAS mutation of pancreatic cancer, we can now begin clinical trials for other cancers that may have KRAS mutation (colorectal, lung) and see if there is success there. If there is success in treating other cancers during clinical trials, it could be fast tracked through FDA to be more generally available and then become part of the national treatment option (ideally in 1-5 years after clinical trials).
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redleggedfrog 22 minutes ago
That was a really good summary, thank you.
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siva7 5 minutes ago
It won't help... mind you this is an article from the economist. There is no such thing as a cancer "master switch", that would equal a disease master switch and that point we have solved biology.
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GaggiX 56 minutes ago
One of the many therapies that are being developed so that you can survive longer even with the most lethal tumours.
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pdar4123 34 minutes ago
Please remember that science is under attack in the United States - new proposals would gut the nih even beyond the horror that is ongoing. As a scientist I am horrified and I truly hope that we don’t abandon the usas historically strong investment in the future.
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gavinray 19 minutes ago
To offer context for others:

The bigger deal about this is that KRAS was considered an "undruggable" target.

Recent advancements have allowed us to design biologics to do things we previously thought impossible, which broadens the horizons for other treatments in the future.

Baby steps.

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ispeters 2 hours ago
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fhdkweig 2 hours ago
The relevant line is:

"oncologists went wild over the results of a drug called daraxonrasib."

https://en.wikipedia.org/wiki/Daraxonrasib

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variety8675 2 hours ago
The study this article references is here: https://clinicaltrials.gov/study/NCT06625320
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an0malous 54 minutes ago
I’m surprised Michael Levin’s research hasn’t expanded much beyond a certain YouTube media bubble. They’re able to start and stop cancer growth with only voltage changes between cells, likewise they can also trigger regeneration or anatomical changes using voltage changes. His research seems to suggest a lot of important anatomical plans are stored in an electric field around the body, not in the DNA. This model’s explanation for cancer is that some cells become disconnected from this field and start growing independently of the overall body plan.
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neonstatic 20 minutes ago
I love his work (even though I know little more than what he says in interviews). I am also surprised it's not more widely known / applied. I am very skeptical of conspiracy-minded thinking, so I'd much rather assume his and his team's work hasn't reached escape velocity from obscurity. Especially with larger industries, it takes time and significant breakthroughs to become "a household name", so to speak.
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DivingForGold 2 hours ago
Thanks for posting useful link !
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